This invention is generally in the field of devices for the administration of drugs to patients through the skin. More particularly, this invention relates to microneedle arrays and methods for transdermal drug delivery.
Transdermal drug delivery provides several advantages over other routes for administering a drug formulation to a patient. For example, oral administration of some drugs may be ineffective because the drug is destroyed in the gastrointestinal tract or eliminated by the liver, both of which are avoided by transdermal drug delivery. Parenteral injection with a conventional hypodermic needle also has drawbacks, as it is often painful and inconvenient. Although transdermal drug delivery avoids these problems, there are obstacles to its use. In particular, the transport of drug molecules through the intact stratum corneum, the outer layer of the skin, is often quite difficult due to the barrier properties of the stratum corneum. These barrier properties only allow relatively small molecules to be transported through the intact stratum corneum, and many useful drugs are too large to pass through the stratum corneum without some type of modification of the stratum corneum or other transport enhancement. Various transdermal enhancement methods are known, including those based on iontophoresis, ultrasound, and chemical penetration enhancers. However, these methods may be inadequate to assist in the delivery of many medications through an intact skin layer and/or they may be inconvenient or undesirably complicated to use.
Several methods have been recently proposed for making small pores in the stratum corneum in order to overcome its barrier properties. For example, patents to Altea Therapeutics disclose the use of arrays of micro-heaters for creating tiny holes in the stratum corneum, as well as the use of miniature pyramidal projections to porate the stratum corneum. See, e.g., U.S. Pat. No. 6,142,939 to Eppstein et al. and U.S. Pat. No. 6,183,434 to Eppstein. Others, including Procter & Gamble, Alza Corporation, and scientists and engineers at the University of California, Berkeley and at the Georgia Institute of Technology, have been working on the development of microneedle arrays that would make a large number of tiny holes in the stratum corneum. See, e.g., U.S. Pat. No. 6,611,707 to Prausnitz et al. and U.S. Pat. No. 6,334,856 to Allen et al.
These known microneedle array generally fall into one of two design categories: (1) solid microneedles and (2) microneedles with a central hollow bore, which are similar to conventional hypodermic needle. Solid microneedle arrays are essentially arrays of projections that are used to make holes in the stratum corneum and are subsequently removed before a drug is applied to the skin. If solid microneedle arrays are kept in the skin, then the drug cannot readily flow into and through the holes in the skin because the holes remain plugged by the microneedles. In an apparent effort to work around this problem, Alza Corporation discloses a method of depositing a drug directly on the surface of these solid microneedles. However, the deposition process is unreliable, and the thin layer of drug formulation on the microneedle could be easily chipped off of the microneedle during storage, transport, or administration (insertion) of the microneedles. Moreover, application of a thicker and stronger layer of drug formulation was found to be undesirable because it reduced the sharpness of the microneedles and therefore made insertion more difficult and painful. In response to this deficiency with the thicker drug coating, Alza Corporation disclosed a special insertion device, because patients are unable to insert the microneedle array by their selves without it. It therefore would be desirable to provide a microneedle array for drug delivery that avoids the disadvantages associated with known solid microneedle array designs.
Conventional hollow microneedles with a central bore are expensive to make and require exotic and expensive microfabrication methods. In particular, it is difficult to make sharp tips on hollow microneedles. Consequently, insertion of the microneedles into a patient's skin can be difficult and often painful. In addition, the central bore of the microneedle is quite small and may be easily plugged by skin tissue during the insertion process, thereby blocking the drug delivery conduit. Furthermore, because the length of microneedle central bore is much greater than its diameter, the diffusional transport of the drug through the central bore may be unacceptably slow. It may be even slower than the diffusion of the drug through the stratum corneum in the absence of the microneedle. It therefore would be desirable to provide a microneedle array for drug delivery that avoids the disadvantages associated with known hollow microneedle array designs.
U.S. Patent Application Publication No. 2003/0028125 discloses devices and methods for piercing the skin and accessing and collecting a physiological fluid sample therein. The disclosed device is unsuitable for drug delivery to the stratum corneum, in particular because the needle design is too large for such applications.
In summary, there is a need for a simple, effective, and economically desirable device for transdermal administration of a variety of drug types to a patient.